Unravelling the magic — the history behind placebos in research

TODAY, we take the use of placebos in clinical trials for granted, often assuming that this is a relatively recent innovation. The truth, however, is more interesting and begins in pre-revolutionary France.

In 1778, Parisians who were sick and rich could try a novel treatment from a charismatic physician called Anton Mesmer who had recently arrived from Vienna. His clinic was in the exclusive Place Vendôme in Paris. There you would enter a dimly-lit room and join others seated in concentric circles. At the centre of the room was a wooden tub filled with ground glass, iron fillings and bottles of magnetised water along with metal rods. You would be invited to hold one of these rods on your affected body part. In the background there would be hushed silence punctuated by the ethereal sounds from the glass harmonica – a newly invented musical instrument sounding like a wet finger stroking the rim of a wine glass.

The scene set, Mesmer would appear in a lilac silk coat carrying a metal wand. He would sit en rapport with some patients – knees touching and gazing intently into their eyes. His assistants, reported to have been young and handsome, would also help the magnetic flux by massaging the knees, backs and breasts of patients. This combination of sensory stimuli caused many patients to become entranced or mesmerised and some to faint or convulse. And, of course, many claimed to be cured.

But what was really happening here? Lighting, music, costume, drama and sensuality – what was going on was more ritual than medicine, more suggestion than treatment, a little more Dumbledore than doctoring. Perhaps in a pre-enlightenment era, this would simply have been viewed as magic. But, this was the 1780s – the world had moved on. Now, this magic had to have a rational scientific basis and Mesmer provided it. He believed magnetic fluid flowed into us from the stars and that disease was the result of an obstruction to this flow. His treatment was designed to realign this animal magnetism.

Mesmer’s treatments soon became the height of fashion, but he was not without critics, and the establishment would have nothing to do with him. Indeed, the King himself stepped in and appointed a commission to investigate, asking the elderly American Ambassador to France to take the lead. This was none other than Benjamin Franklin. Today we remember Franklin as an elder statesman, but in his lifetime he was among the most celebrated scientists and it was in this capacity that the King sought his help.

Franklin and his colleagues devised a series of experiments using placebos for the first time. Subjects were presented with magnetised objects and with sham objects that looked the same but were untreated. The patients were unable to distinguish the two and variably reported the effects. As a result of these placebo-controlled experiments, the commission was able to conclude that there was no basis to Mesmer’s claims. Instead, they explained that animal magnetism “owed its apparent efficacy to the power of suggestion in susceptible or naïve individuals.”

Although the term placebo did not enter medical parlance until 1785, it is clear that for centuries before healers had used remedies they knew to be inactive, but which they also knew would appease their patients. Placebo indeed is Latin for “I shall please”. However, Franklin and the Commissioners are credited with being the first to use placebos in a clinical research setting.

Placebos are now an essential part of modern research, used to prevent confounding from the so-called placebo effect, i.e. the effects that an inactive substance, procedure or device may have when administered in a clinical context over and above the effects observed of no treatment. This effect is complex and still relatively poorly understood, but it is undoubtedly real and can significantly impact our evaluation of different treatments if not taken into account. Whatever the treatment, it may be possible to create a matched, but ineffective alternative to act as a control. Benefit may only be claimed if the active treatment produces significantly greater effect than the placebo.

Thus, without the ingenuity of a group of enlightened French scientists led by an aging American diplomat, perhaps today we would not have the placebo-controlled randomised clinical trial. Perhaps our clinical practice might still be based only on observation and anecdote rather than hard evidence. And perhaps physicians would still have wands.